In health and clinical studies, health-related quality of life is often assessed using the well-established KIDSCREEN-52 questionnaires as well as the Vécu et Santé Perçue de l’Adolescent (VSP-A). The purpose of this study was twofold: to perform an adjusted linguistic validation of the Colombian version of the KIDSCREEN-52 and to assess its psychometric properties in children and adolescents. A total of 146 children and adolescents completed the KIDSCREEN-52, adolescents ( n = 48) additionally completed the VSP-A. Psychometric analyses focused on the internal consistency as well as the convergent and discriminant validity of the KIDSCREEN-52 Colombian version. Syntactic and semantic modifications were made to 19 items in the adapted version of the KIDSCREEN-52. Cronbach’s α ranged from .74 to .89 for eight dimensions, while α < .70 was obtained for self-perception and social acceptance. We found evidence of good convergent validity with the VSP-A dimensions. Regarding known-groups validity, children aged between 8 and 10=years, male, with a high socioeconomic level and no chronic health condition obtained higher scores compared to the other categories. The developed Colombian version of the KIDSCREEN-52 showed acceptable reliability and validity. This study provides a cultural adaptation of the Spanish version of the KIDSCREEN-52 for Colombian children and adolescents.